We will continue to develop methods for the prenatal diagnosis of sickle cell anemia and beta thalassemia. In sickle cell anemia, we will search for other polymorphisms which may be utilized for analysis of the sickle gene so that we may be able to diagnose all cases. We also will search for a polymorphism linked to the beta-thalassemia gene to see if we could utilize this method for prenatal diagnosis. Molecular Mechanisms of Thalassemia: 1. alpha Thalassemia; We will use the molecular cloning techniqque to isolte the alpha thalassemia gene and tocompare the extent of deletion in different populations. 2. Beta Thalassemia; We will try in vitro manipulation with suppressor tRNA and other means to overcome the nonsense mutation.